Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Jan;71(1):55-61.
doi: 10.1001/jamaneurol.2013.4781.

Serum brain-derived neurotrophic factor and the risk for dementia: the Framingham Heart Study

Galit Weinstein  1 , Alexa S Beiser  2 , Seung Hoan Choi  3 , Sarah R Preis  4 , Tai C Chen  5 , Demetrios Vorgas  5 , Rhoda Au  1 , Aleksandra Pikula  1 , Philip A Wolf  1 , Anita L DeStefano  2 , Ramachandran S Vasan  1 , Sudha Seshadri  1
Affiliations

Serum brain-derived neurotrophic factor and the risk for dementia: the Framingham Heart Study

Galit Weinstein et al. JAMA Neurol. 2014 Jan.

Abstract

Importance: In animal studies, brain-derived neurotrophic factor (BDNF) has been shown to impact neuronal survival and function and improve synaptic plasticity and long-term memory. Circulating BDNF levels increase with physical activity and caloric restriction, thus BDNF may mediate some of the observed associations between lifestyle and the risk for dementia. Some prior studies showed lower circulating BDNF in persons with Alzheimer disease (AD) compared with control participants; however, it remains uncertain whether reduced levels precede dementia onset.

Objective: To examine whether higher serum BDNF levels in cognitively healthy adults protect against the future risk for dementia and AD and to identify potential modifiers of this association.

Design, setting, and participants: Framingham Study original and offspring participants were followed up from 1992 and 1998, respectively, for up to 10 years. We used Cox models to relate BDNF levels to the risk for dementia and AD and adjusted for potential confounders. We also ran sensitivity analyses stratified by sex, age, and education, as well as related BDNF genetic variants to AD risk. This community-based, prospective cohort study involved 2131 dementia-free participants aged 60 years and older (mean [SD] age, 72 [7] years; 56% women).

Main outcomes and measures: Ten-year incidence of dementia and AD.

Results: During follow-up, 140 participants developed dementia, 117 of whom had AD. Controlling for age and sex, each standard-deviation increment in BDNF was associated with a 33% lower risk for dementia and AD (P = .006 and P = .01, respectively) and these associations persisted after additional adjustments. Compared with the bottom quintile, BDNF levels in the top quintile were associated with less than half the risk for dementia and AD (hazard ratio, 0.49; 95% CI, 0.28-0.85; P = .01; and hazard ratio, 0.46; 95% CI, 0.24-0.86; P = .02, respectively). These associations were apparent only among women, persons aged 80 years and older, and those with college degrees (hazard ratios for AD: 0.65, [95% CI, 0.50-0.85], P = .001; 0.63 [95% CI, 0.47-0.85], P = .002; and 0.27 [95% CI, 0.11-0.65], P = .003, respectively). Brain-derived neurotrophic factor genetic variants were not associated with AD risk.

Conclusions and relevance: Higher serum BDNF levels may protect against future occurrence of dementia and AD. Our findings suggest a role for BDNF in the biology and possibly in the prevention of dementia and AD, especially in select subgroups of women and older and more highly educated persons.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure
Figure
Cumulative Incidence of Alzheimer Disease by Quintiles of Serum Brain-Derived Neurotrophic Factor Levels
See this image and copyright information in PMC

Comment in

References

    1. Seshadri S, Wolf PA. Lifetime risk of stroke and dementia: current concepts, and estimates from the Framingham Study. Lancet Neurol. 2007;6(12):1106–1114. - PubMed
    1. Ferri CP, Prince M, Brayne C, et al. Alzheimer’s Disease International. Global prevalence of dementia: a Delphi Consensus Study. Lancet. 2005;366(9503):2112–2117. - PMC - PubMed
    1. Lee J, Seroogy KB, Mattson MP. Dietary restriction enhances neurotrophin expression and neurogenesis in the hippocampus of adult mice. J Neurochem. 2002;80(3):539–547. - PubMed
    1. Neeper SA, Gómez-Pinilla F, Choi J, Cotman C. Exercise and brain neurotrophins. Nature. 1995;373(6510):109. - PubMed
    1. Vaynman S, Ying Z, Gomez-Pinilla F. Interplay between brain-derived neurotrophic factor and signal transduction modulators in the regulation of the effects of exercise on synaptic-plasticity. Neuroscience. 2003;122(3):647–657. - PubMed

Publication types

MeSH terms

Substances